Equatorial epoxides

Stereoselective epoxidation can be realized through either substrate-controlled (e.g. 35 —> 36) or reagent-controlled approaches. A classic example is the epoxidation of 4-t-butylcyclohexanone. When sulfonium ylide 2 was utilized, the more reactive ylide irreversibly attacked the carbonyl from the axial direction to offer predominantly epoxide 37. When the less reactive sulfoxonium ylide 1 was used, the nucleophilic addition to the carbonyl was reversible, giving rise to the thermodynamically more stable, equatorially coupled betaine, which subsequently eliminated to deliver epoxide 38. Thus, stereoselective epoxidation was achieved from different mechanistic pathways taken by different sulfur ylides. In another case, reaction of aldehyde 38 with sulfonium ylide 2 only gave moderate stereoselectivity (41 40 = 1.5/1), whereas employment of sulfoxonium ylide 1 led to a ratio of 41 40 = 13/1. The best stereoselectivity was accomplished using aminosulfoxonium ylide 25, leading to a ratio of 41 40 = 30/1. For ketone 42, a complete reversal of stereochemistry was observed when it was treated with sulfoxonium ylide 1 and sulfonium ylide 2, respectively. ... 

Recendy, Darzens reaction was investigated for its synthetic applicability to the condensation of substituted cyclohexanes and optically active a-chloroesters (derived from (-)-phenylmenthol). In this report, it was found that reaction between chloroester 44 and cyclohexanone 43 provided an 84% yield with 78 22 selectivity for the axial glycidic ester 45 over equatorial glycidic ester 46 both having the R configuration at the epoxide stereocenter. 

Epoxides from aldehydes, 46, 44 Equatorial alcohols, preparation by use of the lithium aluminum hydride-aluminum chloride reagent, 47, 19... 

Klein showed that axial reaction of the parent methylenecyclohexane 37 is preferred in hydroboration [106], The experimental data on the parent methylenecyclohexanone 37a accumulated by Senda et al. [107] and the more recent systematic studies by Cieplak et al. [108, 109] on jr-facial selectivities of 3-substituted methylene-cyclohexanes 37 have characterized the intrinsic features of the facial selection of methylenecyclohexanes. That is, axial preference of unsubstituted and 3-substituted methylenecyclohexanes was observed in oxymercuration [107] and epoxidation reactions [110], There is also an increase in the proportion of axial attack with increase in the electronegativity of the remote 3-equatorial... 

Another difference between dimethylsulfonium methylide and dimethylsulfoxonium methylide concerns the stereoselectivity in formation of epoxides from cyclohexanones. Dimethylsulfonium methylide usually adds from the axial direction whereas dimethylsulfoxonium methylide favors the equatorial direction. This result may also be due to reversibility of addition in the case of the sulfoxonium methylide.92 The product from the sulfonium ylide is the result the kinetic preference for axial addition by small nucleophiles (see Part A, Section 2.4.1.2). In the case of reversible addition of the sulfoxonium ylide, product structure is determined by the rate of displacement and this may be faster for the more stable epoxide. 

Figure 19. Perpendicularity of the PAH and the base. Conformations of trans-diols. The steric hindrance in a bay region will cause hydroxyl or other substituents (such as DNA) to lie in an axial orientation. Sites where this occurs are marked "a". Those sites where there is no steric hindrance are marked "ae" (axial or equatorial). The conclusion is that when a diol epoxide alkylates DNA the base on DNA will be bonded axially to the PAH group.

Access to P-mannosides [209] is illustrated by the preparation of 179 from P-glucoside 178 by oxidation of the equatorial 2-OH followed by stereoselective reduction to give the axial alcohol an efficient indirect route to the a-mannosides [206] utilizes the P-thioglucoside 182, readily obtained from epoxide 173, proceeding via an oxidation-reduction protection sequence to give P-thiomannoside glycosyl donor 184, from which a-mannoside 185 can be stereoselectively prepared. 

When the water ligand of 5b is replaced by propenol as axial donor or in case of equatorial coordination of propenol at the metal center, intermediates are formed which could undergo intramolecular epoxidation through TSs S-6 and S-7b, respectively (Figure 11). Here, the prefix S indicates a transition... 

Optically pure P-ethanolamines react with dichlorocarbene under phase-transfer catalytic conditions to produce epoxides of high configurational retention [30]. Initial reaction occurs at the tertiary nitrogen centre (Scheme 7.29) with subsequent cleavage of the C-N bond. The reaction is configurationally controlled, as shown by the reaction of the conformationally rigid cyclic systems epoxide formation occurs with the equatorial hydroxyl system (50%), but not with the axial hydroxyl compound. 

The origin of stereofacial selectivity in electrophilic additions to methylene-cyclohexanes (2) and 5-methylene-l,3-dioxane (3) has been elucidated experimentally (Table 2) and theoretically. Ab initio calculations suggest that two electronic factors contribute to the experimentally observed axial stereoselectivity for polarizable electrophiles (in epoxidation and diimide reduction) the spatial anisotropy of the HOMO (common to both molecules) and the anisotropy in the electrostatic potential field (in the case of methylenedioxane). The anisotropy of the HOMO arises from the important topological difference between the contributions made to the HOMO by the periplanar p C-H a-bonds and opposing p C—O or C—C cr-bonds. In contrast, catalytic reduction proceeds with equatorial face selectivity for both the cyclohexane and the dioxane systems and appears to be governed largely by steric effects. ... 

Note also that, although we normally see rapid inversion at a nitrogen atom, the Al-methyl gronp in hyoscyamine is preferentially in the lower energy equatorial position of the chair-like piperidine ring, as wonld be predicted. However, in hyoscine, the Al-methyl group has been found to be axial, not the expected eqnatorial. This seems to arise to minimize interaction with the extra epoxide ring in scopine. 

A number of studies have now been made, notably by Buchanan and coworkers, with the object of determining the position of the equilibrium between the various pairs of interconvertible epoxides the findings are summarized in Chart I. For the dianhydro compounds, the epoxides that contain the free hydroxyl group quasi-axial, and that also have the possibility of a polar interaction between the epoxide ring and the 1,6-anhydro bridge, are clearly less stable than those in which it is quasi-equatorial, although the relative importance of these two factors is uncertain. The situation is less clear for the monocyclic epoxides. The half-chair conformations indicated are considered to be favored on the basis that the alkyl... 

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